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Journal Articles

Model development for estimating effects of boron neutron capture therapy

Fukunaga, Hisanori*; Matsuya, Yusuke

Hoshasen Seibutsu Kenkyu, 56(2), p.208 - 223, 2021/06

Boron Neutron Capture Therapy (BNCT) is one of the radiation therapies, enabling selectively eradicating tumors by short-range a-particles and Li ions generated through the nuclear reaction between thermal neutron and $$^{10}$$B within tumor cells. With the development of the accelerator-based neutron source in the recent decades, it is expected that BNCT will be available in many medical facilities worldwide in the future. BNCT irradiation needs a relatively long dose-delivery time after taking up boron drug into tumor cells by intravenous injection. During the period, it is suspected that the boron drug is heterogeneously taken up into cells and its concentration changes continuously, leading to the modification of curative effects from the pharmacological and biological viewpoints. However, the model development for precisely predicting curative effects after BNCT irradiation is still ongoing. Here, we introduce the forefront of model development for estimating the curative effects during BNCT irradiation with high accuracy. This review can create the synergetic effects through an interdisciplinary research approach that can connect the fields of physics, pharmacology, biology and medicine, and would pave the way for new era of BNCT.

Journal Articles

Implications of radiation microdosimetry for accelerator-based boron neutron capture therapy; A Radiobiological perspective

Fukunaga, Hisanori*; Matsuya, Yusuke; Tokuue, Koichi*; Omura, Motoko*

British Journal of Radiology, 93(1111), p.20200311_1 - 20200311_4, 2020/07

 Times Cited Count:0 Percentile:0.02(Radiology, Nuclear Medicine & Medical Imaging)

Boron neutron capture therapy (BNCT) has attracted attention as a selective treatment approach for cancer cells while sparing surrounding normal cells. The basic concept of BNCT was developed in the 1930s, but it has not yet been commonly popular in clinical practice, even though there is now a large number of experimental and translational studies demonstrating its marked therapeutic potential. With the development of neutron accelerators that can be installed in medical institutions, accelerator-based BNCT is expected to become available at several medical institutes around the world in the near future. In this commentary, from the point of view of microdosimetry, we discuss the biological effects of BNCT, especially the underlying mechanisms of cell responses. The recent development of new treatment methods that combine proton beam sources and BNCT technology is expected to contribute significantly improving the prognosis of cancer treatment in the near future. Therefore, radiobiologists in the field of BNCT and related techniques will have a significant role to play in creating synergy effects in clinical oncology.

Journal Articles

A Model for estimating dose-rate effects on cell-killing of human melanoma after boron neutron capture therapy

Matsuya, Yusuke; Fukunaga, Hisanori*; Omura, Motoko*; Date, Hiroyuki*

Cells, 9(5), p.1117_1 - 1117_16, 2020/05

 Times Cited Count:5 Percentile:67.45(Cell Biology)

When delivering a high absorbed dose to cancer cells following boron neutron capture therapy (BNCT), heterogeneous dose distribution, the time line of $$^{10}$$B concentrations and the long dose-delivery time must be considered. Changes in radiosensitivity during such a long dose-delivery time can reduce the probability of tumor control; however, such change has not yet been evaluated. Here, we developed a cell-killing model that accounts for changes in microdosimetric quantities and dose rates depending on the $$^{10}$$B concentration and investigated dose-rate effects (cell recovery during BNCT irradiation) of melanoma. The developed model shows good agreement with in-vitro experimental survival data for exposure to $$^{60}$$Co $$gamma$$-rays, thermal neutrons, and BNCT. The model estimation suggests that the impact of cell recovery during BNCT irradiations with high linear energy transfer (LET) is reduced compared to $$^{60}$$Co $$gamma$$-rays irradiation with low LET. The present model is expected to predict radio-sensitivity for BNCT irradiations.

Journal Articles

Low-dose radiation risk and individual variation in radiation sensitivity in Fukushima

Fukunaga, Hisanori*; Yokoya, Akinari

Journal of Radiation Research, 57(1), p.98 - 100, 2016/01

 Times Cited Count:7 Percentile:87.92(Biology)

Oral presentation

Development of a model to predict BNCT therapeutic effects in consideration of intracellular boron concentration and DNA repair during neutron irradiation

Matsuya, Yusuke; Omura, Motoko*; Fukunaga, Hisanori*

no journal, , 

Boron neutron capture therapy (BNCT) is a treatment method enabling selectively eradicating tumors by $$alpha$$-particles and Li ions generated through the nuclear reaction between neutrons and $$^{10}$$B within tumor cells. While the accelerator-based neutron source has been developed, the intracellular $$^{10}$$B concentration dynamically changes after intravenous injection of the boron into patients, and the neutron-delivery time is relatively long for 30 minutes or more. However, the quantitative analysis for investigating the impacts of DNA repair during irradiation on curative effects is insufficient. In this study, we developed a mathematical model for predicting the therapeutic effects that considers the change in intracellular $$^{10}$$B concentration and DNA repair, and performed detailed analysis. The model developed in this study considers the following two factors: one is microdosimetric quantities (physical characteristics) that depends on $$^{10}$$B concentration, and the other is DNA repair dynamics (biological process) during irradiation. The model estimation results exhibits that the importance of DNA repair during irradiation is reduced in the case of BNCT with a higher dose at sub-cellular scale than photons. It was also suggested that the DNA repair effects on tumor control cannot be ignored even in the case of BNCT. In the future, further accumulation of radiobiological data is desired for improving models.

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